Johannes von Lintig, Ph.D.

Associate Professor with Tenure, Pharmacology

Research

Carotenoids affect a rich variety of physiological functions in nature and are beneficial
for human health, serving as antioxidants in lipophilic environments and blue light
filters in the macula of the human retina. These dietary compounds also are the
natural precursors for retinoids (vitamin A and its derivatives) that play critical
roles for vision and gene regulation. To establish and sustain retinoid-dependent
physiological processes, these compounds must be absorbed in the intestine, transported
in the body, metabolized to biologically active compounds such as 11-cis-retinal
and all-trans-retinoic acid. Vitamin A deficiency is still a major health problem
in developing countries. Moreover, mutations of genes encoding the involved components
have emerged as important causes for not only blinding diseases but also fatal diseases
such as the Matthew-Wood syndrome, characterized by pleiotropic, multisystem malformations
that include cardiac deformities and ocular defects. Although knowledge about retinoid
biology has significantly increased, many aspects remain poorly understood, including
the metabolism of retinoids’ parent precursors the carotenoids.

Our laboratory has
molecularly identified and biochemically characterized key players of carotenoid
metabolism, including the vitamin A forming enzyme. Our approaches include structure-function
analysis of these proteins, studies cell culture models, and the establishment of
disease-relevant animal models for the analysis of the consequences of their loss
of function. Further, we are addressing the question how the supply of carotenoids
and retinoids to tissues is regulated to avoid excess and deficiency, which both
can have deleterious consequences and can cause disease. Additionally, we are working
on questions concerning ocular retinoid metabolism and the putative role of retinoids
in retinal damage. We hope that our research will contribute to a better molecular
and mechanistic understanding of carotenoid and retinoid metabolism in health and
disease.